Hudig: Muscosal Immunity

Question 1

What is included in the GALT?

Answer 1

tonsils
stomach
small intestine
colon

Question 2

What happens to food in the small intestine?

Answer 2

it is absorbed & carried via hepatic portal vein to the liver

Question 3

What are the endocrine cells located in the crypts?

Answer 3

paneth cells

Question 4

What are the cells that secrete mucus into the lumen?

Answer 4

goblet cells

Question 5

Are food molecules recognized as foreign antigens?

Answer 5

no, rarely!

Question 6

Enterocytes secrete (blank)

Answer 6

β-defensins

Question 7

The paneth cells secrete (blank)

Answer 7

alpha-defensins

Question 8

Mucins and (blank) bind each other, which keeps the defensins in place and concentrated so they can kill bacteria.

Answer 8

defensins

Question 9

These two components are essential to innate immunity

Answer 9

mucins & defensins

Question 10

These cells allow antigens to cross from the gut into the system

Answer 10

M cells

Question 11

What do dendritic cells do?

Answer 11

secrete different cytokines to determine how the T cells differentiate –> TH2, TH1, Tregs

Question 12

Mucosal B sells secrete these two antibodies

Answer 12

IgM & IgA

Question 13

How much IgA is secreted per day?

Answer 13

3-4 grams!

Question 14

Where are M cells located? What do they do?

Answer 14

above the peyer’s patches - they carry in antigens, whole proteins & bacteria, which can then bind to dendritic cells & go on to activate T cells

Question 15

M cells are highly specialized for (blank)

Answer 15

antigen

Question 16

Which MHC do DC cells use for antigen presentation? What regulatory cells respond?

Answer 16

MHC II; all CD4 cells

Question 17

What do T-regs produce to shut down all T & B cell responses to antigen? What is their purpose in the gut?

Answer 17

IL-10 & TGF-beta; to shut down immune responses before they even begin

Question 18

What does it take to get an induced T reg?

Answer 18

a dendritic cell on the other end of the M cell that is getting a lot of TGF-beta as a signal

Question 19

What is lymphocyte homing?

Answer 19

Lymphocytes recognize addressins, like MADCAM1, and adhesion molecules that are selectively expressed in the GI. These addressins & adhesion molecules are recognized by integrins on the lymphocytes in the mucosa.
Chemokines are also involved as attractors.

Question 20

What is one example of a mucosa specific chemokine?

Answer 20

CCL25

Question 21

What are examples of addressins in the gut?

Answer 21

E-cadherin

MADCAM1

Question 22

Lymphocytes have receptors that can recognize the (blank) in the gut

Answer 22

chemokines

Question 23

Different cells are present in different parts of the villi. For example, (blank) cells are located in the epithelium only because there are E-cadherins there. There are lots of different cells in the lamina propria. Give some examples.

Answer 23

CD8 T cells (waiting in the epithelium to destroy cells that become virally infected)
plasma cells & macrophages, etc

Question 24

(blank) are CTLs ready to kill, to eliminate viruses

Answer 24

memory CD8 intraepithelial lymphocytes

Question 25

Which cytokine from DCs induces lymphocytes to become T regs?

Answer 25

TGF-beta

Question 26

The only antibodies transported into the gut...

Answer 26

IgM & IgA

Question 27

What do TH17 cells do?!

Answer 27

they secrete IL-17, which ultimately brings in neutrophils they act on fibroblasts, which secrete chemokines that bring in neutrophils!!! **fibroblasts are good guys in the gut

Question 28

What is the problem in celiac disease?

Answer 28

damaged villi in the small intestine

Question 29

What are the symptoms of celiac disease?

Answer 29

``` chronic diarrhea weight loss abdominal pain & distention malabsorption of iron & Vit B12 megaloblastic anemia FTT ```

Question 30

What happens to the villi & crypts in celiac disease?

Answer 30

shortened villi (can't absorb nutrients) & crypt hyperplasia

Question 31

What is one antibody you look for to diagose celiac disease? What is one caveat to this test?

Answer 31

IgA auto-antibodies to tissue transglutaminase 2 | **must have been exposed to gluten in the last 2 wks for a positive test

Question 32

What other antibodies may be present?

Answer 32

Serum IgA antibody to de-amidated gliadin **this is an altered wheat protein

Question 33

This is one antibody that is not unique to celiac pts, but can be present

Answer 33

Serum IgA auto-antibodies to EMA (endomysium antigens)

Question 34

What alleles can be associated with celiac disease?

Answer 34

HLA DQ2 & DQ8

Question 35

What is essential for the diagnosis of celiac disease?

Answer 35

biopsy! **pt must have been exposed to wheat in the 2 wks prior

Question 36

Do pts with celiac disease have IgE allergy to gluten?

Answer 36

nooo - that is a different thing

Question 37

What will you see on endoscopy & biopsy in a celiac pt?

Answer 37

scalloping of the mucosal folds | loss of villous architecture, truncated villi

Question 38

How to treat celiac disease?

Answer 38

gluten-free diet (no wheat, barley or rye) **even micrograms of gluten can trigger disease

Question 39

How many intraepithelial lymphocytes are found per 100 enterocytes in celiac disease?

Answer 39

great than 25 per 100!

Question 40

In celiac disease, CD8 IELs also have (blank) receptors, which respond to stress, as opposed to a specific antigen

Answer 40

NK

Question 41

What is one potential therapy for celiac disease?

Answer 41

mAbs to block either of 2 T cell mucosal integrins or a MALT chemokine receptor

Question 42

affects both ileum and colon | associated with defects of defensins

Answer 42

Chron's disease

Question 43

affects only colon | associated with defects of mucus

Answer 43

ulcerative colitis

Question 44

Crohn’s disease may have lower (blank) recruitment | than warranted for protection….

Answer 44

neutrophil

Question 45

Clinically, (blank) tends to present more frequently with abdominal pain and perianal disease, whereas (blank) is more often characterized by gastrointestinal bleeding

Answer 45

Crohn's disease; ulcerative colitis

Question 46

Cobblestoning mucosa and aphthous or linear ulcers characterize the endoscopic appearance of this disease

Answer 46

Crohn's disease

Question 47

So compare & contast Crohn's & ulcerative colitis

Answer 47

Crohn's: throughout GI, lack of defensins, cobblestoning ulcerative colitis: colon, lack of mucous

Question 48

(blank) can induce remission in Crohn's disease

Answer 48

rifaximin **antibiotic - this suggests that there is a bacterial factor to this disease

Question 49

Limited to colon Damage extends only to mucosa and submucosa, no deeper Implication of low mucus But normal Paneth cell defensins

Answer 49

ulcerative colitis

Question 50

3 immune imbalances that can contribute to Crohn's disease?

Answer 50

1. low antimicrobial peptides (defensins) 2. more live bacterial antigen 3. more TH1 & T17 cells OR fewer T-regs to dampen response